1,721,024 research outputs found
Expression and role of hERG1 channels in pediatric acute lymphoblastic Leukemias: Shortcoming of drug resistance by hERG1 channel inhibitors in stoma-supported leukaemia cell cultures in vitro.
No full textTherapy resistance is still a major obstacle to successful treatment in a significant number of pediatric acute lymphoblastic leukaemia (ALL) patients. It has been previously demonstrated that children with ALL whose leukemia cells exhibit in vitro resistance to single or a combination of drugs have a significantly worse prognosis compared to patients with sensitive leukemic cells (Ramakers-van Woerden N, et al Leukemia 18(3):521–9 2004[Medline]). Ion channels are becoming one of the potential targets for cancer therapy and putative biochemical modulators of conventional chemotherapy (Conti M, J Exp Ther Oncol. 4(2):161–6, 2004[Medline]). In particular, K+ channels belonging to the hERG1 family are attracting most attention, since they are over-expressed in a broad range of primary acute myeloid leukaemias (AML) as well as in both myeloid and lymphoid leukemic cell lines (Pillozzi S, et al Leukemia 16:1791–1798, 2002[Medline]; Smith GA, et al, JBC 227:18528–18534, 2002). hERG1 channel expression confers a greater capacity to engraft the bone marrow and invade the bloodstream in NOD/SCID mice injected with AML cells. This fact corresponds to a greater malignancy (shorter overall survival and higher probability to relapse) in hERG1 positive AML patients (Pillozzi S, et al Blood 110:1238–1250, 2007[Abstract/Free Full Text]). It was also recently shown that the expression of hERG1 is related to the chemosensitivity of cancer cells to vincristine, paclitaxel, and hydroxy-camptothecin (Chen SZ, et al Cancer Chemother Pharmacol 56(2):212–20, 2005[Medline]). We studied the expression and role of hERG1 channels in various B lymphoid leukaemia cell lines and primary childhood B lymphoid leukaemia samples. It emerged that:
hERG1 K+ channels are expressed in both all the leukaemia cell lines and primary childhood B leukaemia samples;
the N-terminus deleted, herg1b isoform was preferentially expressed in both cell lines and primary samples;
in childhood leukaemia patients, the level of herg1b expression correlated with response to therapy.
B lymphoid leukaemia cell lines were co-cultured on human bone marrow stromal cells, a system known to enhance leukaemia cell survival and escape from drug-induced apoptosis. In these cultures, the addition of a specific hERG1 inhibitor, E4031, induced a significant apoptosis in leukaemia cells, bypassing the protective effect of the bone marrow microenvironment. We hypothesise that hERG1 channels can represent a novel molecular device regulating drug sensitivity in childhood acute leukaemia cells, and that targeting of hERG1 channels can restore a proper pro-apoptotic response to chemotherapy in resistant B lymphoid leukemic cells
Practical tips and new trends in electrochemical biosensing of cancer-related extracellular vesicles
No full textTo tackle cancer and provide prompt diagnoses and prognoses, the constantly evolving biosensing field is continuously on the lookout for novel markers that can be non-invasively analysed. Extracellular vesicles (EVs) may represent a promising biomarker that also works as a source of biomarkers. The augmented cellular activity of cancerous cells leads to the production of higher numbers of EVs, which can give direct information on the disease due to the presence of general and cancer-specific surface-tethered molecules. Moreover, the intravesicular space is enriched with other molecules that can considerably help in the early detection of neoplasia. Even though EV-targeted research has indubitably received broad attention lately, there still is a wide lack of practical and effective quantitative procedures due to difficulties in pre-analytical and analytical phases. This review aims at providing an exhaustive outline of the recent progress in EV detection using electrochemical and photoelectrochemical biosensors, with a focus on handling approaches and trends in the selection of bioreceptors and molecular targets related to EVs that might guide researchers that are approaching such an unstandardised field
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Drug-induced glutamine depletion hinders the growth of beta- catenin mutated human liver cancer xenografts
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Soft tissue sarcoma: An insight on biomarkers at molecular, metabolic and cellular level
Full text linkSoft tissue sarcomas (STSs) are a heterogeneous group of rare tumors. Although constituting only 1% of all human malignancies, STSs represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. Over 100 histologic subtypes have been characterized to date (occurring predominantly in the trunk, extremity, and retroperitoneum), and many more are being discovered due to molecular profiling. STS mortality remains high, despite adjuvant chemotherapy. New prognostic stratification markers are needed to help identify patients at risk of recurrence and possibly apply more intensive or novel treatments. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the most relevant cellular, molecular and metabolic biomarkers for STS, and highlight advances in STS-related biomarker research
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Insights into the structure/function of HGF/SF from studies with individual domains.
No full textHepatocyte growth factor/scatter factor (HGF/SF), the ligand for the receptor tyrosine kinase encoded by the c-Met proto-oncogene, is a multidomain protein structurally related to the pro-enzyme plasminogen and with major roles in development, tissue regeneration and cancer. We have expressed the N-terminal (N) domain, the four kringle domains (K1 to K4) and the serine proteinase homology domain (SP) of HGF/SF individually in yeast or mammalian cells and studied their ability to: (i) bind the Met receptor as well as heparan sulphate and dermatan sulphate co-receptors, (ii) activate Met in target cells and, (iii) map their binding sites onto the beta-propeller domain of Met. The N, K1 and SP domains bound Met directly with comparable affinities (K(d)=2.4, 3.3 and 1.4 microM). The same domains also bound heparin with decreasing affinities (N>K1>>SP) but only the N domain bound dermatan sulphate. Three kringle domains (K1, K2 and K4) displayed agonistic activity on target cells. In contrast, the N and SP domains, although capable of Met binding, displayed no or little activity. Further, cross-linking experiments demonstrated that both the N domain and kringles 1-2 bind the beta-chain moiety (amino acid residues 308-514) of the Met beta-propeller. In summary, the K1, K2 and K4 domains of HGF/SF are sufficient for Met activation, whereas the N and SP domains are not, although the latter domains contribute additional binding sites necessary for receptor activation by full length HGF/SF. The results provide new insights into the structure/function of HGF/SF and a basis for engineering the N and K1 domains as receptor antagonists for cancer therapy
- …
